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基因活性谱——在评估复杂环境混合物潜在致癌性中的应用。

Genetic activity profiles--application in assessing potential carcinogenicity of complex environmental mixtures.

作者信息

Waters M D, Claxton L D, Stack H F, Graedel T E

机构信息

U.S. Environmental Protection Agency, Genetic Toxicology Division, Research Triangle Park, NC 27711.

出版信息

IARC Sci Publ. 1990(104):75-88.

PMID:2228145
Abstract

Some knowledge of the potential genetic activity of a complex environmental mixture may be gained from an assessment of the genetic activity of its component chemicals. The expanded genetic activity profile (GAP) data-base provides a computer-generated graphic representation of genetic bioassay data as a function of dose of the substance tested. In addition, the atmospheric chemical compound (ACC) data-base contains information on chemical structures, properties, detection methods and sources of chemicals found in ambient air. Using the combined data-bases, information on the quantity of an individual chemical present within a mixture or fraction of a mixture may be related to the quantity (lowest effective dose; LED) of the chemical required to demonstrate a positive response in one or more genetic bioassays. Alternatively, quantitative information on the carcinogenic potency of each individual compound (TD50 value) may be related to the quantity present in the mixture or mixture fraction and used to calculate the percent human exposure dose/rodent potency dose (HERP) for the chemical. Using an additivity assumption, a conservative estimate of potential carcinogenic hazard for the mixture may be calculated based on the HERP indices for its chemical components. This conceptual approach is limited by the relatively small number of chemicals identified in complex mixtures for which genetic toxicology and animal cancer data exist.

摘要

通过评估复杂环境混合物中各成分化学物质的遗传活性,可获得有关该混合物潜在遗传活性的一些知识。扩展的遗传活性谱(GAP)数据库提供了一种计算机生成的图形表示,展示了遗传生物测定数据随受试物质剂量的变化情况。此外,大气化合物(ACC)数据库包含有关环境空气中发现的化学物质的化学结构、性质、检测方法和来源的信息。利用这些组合数据库,混合物中或混合物某一部分中单个化学物质的含量信息,可与在一项或多项遗传生物测定中显示阳性反应所需的该化学物质的量(最低有效剂量;LED)相关联。或者,关于每种化合物致癌效力的定量信息(TD50值)可与混合物或混合物部分中该化合物的含量相关联,并用于计算该化学物质的人类暴露剂量/啮齿动物效力剂量百分比(HERP)。采用相加性假设,可根据混合物化学成分的HERP指数计算出该混合物潜在致癌风险的保守估计值。这种概念性方法受到复杂混合物中已知遗传毒理学和动物癌症数据的化学物质数量相对较少的限制。

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